A Randomized Controlled Trial to Assess the Effect of Lidocaine Administered via Throat Spray and Nebulization in Patients with Refractory Chronic Cough

Rayid Abdulqawi, Imran Satia, Yoshihiro Kanemitsu, Saifudin Khalid, Kimberley Holt, Rachel Dockry, Ashley A. Woodcock, Jaclyn A. Smith

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Abstract

Background: Refractory chronic cough (RCC) is a debilitating condition for which there are no licensed treatments. Lidocaine is a nonselective inhibitor of voltage-gated sodium channels with potential antitussive effects, but randomized placebo-controlled studies evaluating its efficacy in RCC are lacking. Objective: To investigate the efficacy of nebulized lidocaine and lidocaine throat spray versus matched placebos in RCC. Methods: This was a randomized, double-blind, double-dummy, placebo-controlled, 3-way crossover study, comparing the effect of single doses of nebulized lidocaine with lidocaine delivered by a throat spray and matched placebo. The primary end point was cough frequency over the 10 hours following treatment. Secondary end points were visual analog scale scores for urge-to-cough and cough severity; an exploratory analysis evaluated hourly cough rates up to 5 hours after treatment. Results: Twenty-six subjects with RCC were recruited (22 females; mean age, 53.5 ± 12.1 years; FEV 1 %predicted, 105.2 ± 16.8 L; forced vital capacity %predicted, 112.4 ± 18 L). Lidocaine throat spray, but not nebulized lidocaine, significantly reduced 10-hour cough frequency as compared with placebo (throat spray, 22.6 coughs/h; nebulization, 26.9 coughs/h; and placebos, 27.6 coughs/h; P =.04,). Lidocaine throat spray showed the greatest effect on cough compared with placebo in the first hour after administration (31.7 coughs/h vs 74.2 coughs/h; P =.004). Both nebulizer and spray treatments significantly alleviated urge-to-cough and cough severity visual analog scale scores compared with placebo (P <.05). There were no serious adverse events associated with lidocaine therapy. Conclusions: Lidocaine throat spray was effective in reducing cough frequency in patients with RCC. Voltage-gated sodium channel inhibitors applied to pharynx have potential as therapies for RCC.

Original languageEnglish
Pages (from-to)1640-1647
Number of pages8
JournalThe Journal of Allergy and Clinical Immunology: In Practice
Volume9
Issue number4
DOIs
Publication statusPublished - 7 Apr 2021

Keywords

  • Lidocaine
  • Refractory chronic cough
  • Sensory afferents
  • Voltage-gated sodium channels

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